Metabolomics as a Novel Approach for Early Diagnosis of Pediatric Septic Shock and Its Mortality

Mickiewicz, Beata; Vogel, Hans J.; Wong, Hector R.; Winston, Brent W.

doi:10.1164/rccm.201209-1726oc

Cited by 167 publications

(192 citation statements)

References 48 publications

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“…In particular, in our study the presence of acetone ketone bodies in the urine of the septic group suggests a compensatory reaction to a reduced level of ATP. It is interesting to see that also in works on metabolomics in the literature, conducted both on animals and humans, there were increases in metabolites (in plasma and urine) which are part of the oxidative metabolism of fatty acids, such as the ketone bodies (hydroxybutyrate, acetoacetate), in septic subjects [8,[10][11][12]. Lin et al suggest that the increase in acetoacetate and hydroxybutyrate in septic rats may be correlated with major oxidation of fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Urinary 1H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis

Fanos¹,

Caboni²,

Corsello³

et al. 2014

Early Human Development

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The purpose of this article is to study one of the most significant causes of neonatal morbidity and mortality: neonatal sepsis. This pathology is due to a bacterial or fungal infection acquired during the perinatal period. Neonatal sepsis has been categorized into two groups: early onset if it occurs within 3-6 days and late onset after 4-7 days. Due to the not-specific clinical signs, along with the inaccuracy of available biomarkers, the diagnosis is still a major challenge. In this regard, the use of a combined approach based on both nuclear magnetic resonance ( 1 H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques, coupled with a multivariate statistical analysis, may help to uncover features of the disease that are still hidden. The objective of our study was to evaluate the capability of the metabolomics approach to identify a potential metabolic profile related to the neonatal septic condition. The study population included 25 neonates (15 males and 10 females): 9 (6 males and 3 females) patients had a diagnosis of sepsis and 16 were healthy controls (9 males and 7 females). This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05).

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Section: Discussionmentioning

confidence: 99%

Urinary 1H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis

Fanos¹,

Caboni²,

Corsello³

et al. 2014

Early Human Development

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“…The metabolites, which may arise from resident or infecting microorganisms or their hosts, have yielded important information about the pathophysiology of many conditions. Metabolites identified by proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectroscopy (LC-MS) have been used to establish diagnosis and prognosis of many infectious and noninfectious diseases (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Metabolomics, as with the other "omics," is made possible only because advanced analytics are now available.…”

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confidence: 99%

Metabolomics: Applications and Promise in Mycobacterial Disease

Mirsaeidi

Banoei²,

Winston

et al. 2015

Annals ATS

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Until recently, the study of mycobacterial diseases was trapped in culture-based technology that is more than a century old. The use of nucleic acid amplification is changing this, and powerful new technologies are on the horizon. Metabolomics, which is the study of sets of metabolites of both the bacteria and host, is being used to clarify mechanisms of disease, and can identify changes leading to better diagnosis, treatment, and prognostication of mycobacterial diseases. Metabolomic profiles are arrays of biochemical products of genes in their environment. These complex patterns are biomarkers that can allow a more complete understanding of cell function, dysfunction, and perturbation than genomics or proteomics. Metabolomics could herald sweeping advances in personalized medicine and clinical trial design, but the challenges in metabolomics are also great. Measured metabolite concentrations vary with the timing within a condition, the intrinsic biology, the instruments, and the sample preparation. Metabolism profoundly changes with age, sex, variations in gut microbial flora, and lifestyle. Validation of biomarkers is complicated by measurement accuracy, selectivity, linearity, reproducibility, robustness, and limits of detection. The statistical challenges include analysis, interpretation, and description of the vast amount of data generated. Despite these drawbacks, metabolomics provides great opportunity and the potential to understand and manage mycobacterial diseases.

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“…NMR, GC-MS and LC-MS analyses have shown that metabolomic fingerprints (metabolic biopatterns) can be used to differentiate between patients with various diseases and healthy subjects [31, 51-54, 68, 69, 76]. Additionally, 1 H NMR metabolomic analysis has also been shown to be capable of predicting mortality in children and adults with sepsis [15,32]. These studies show that the metabolomic identification of new biomarkers or biopatterns for critical care diseases and syndromes is achievable.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, we investigated whether a metabolomics approach could be useful in the diagnosis and prognosis of septic shock in pediatric intensive care units (PICUs) [32]. We were able to successfully separate metabolic profiles of PICU septic shock patients from non-infected PICU patients (patients with systemic inflammatory response syndrome but not suspected of having an infection) and healthy children.…”

Section: Application Of Nmr-based Metabolomicsmentioning

confidence: 99%

Metabolomics in critical care medicine: a new approach to biomarker discovery

Banoei¹,

Donnelly²,

Mickiewicz³

et al. 2014

CIM

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Metabolomics in critical care medicine: a new approach to biomarker discovery Abstract Purpose: To present an overview and comparison of the main metabolomics techniques ( 1 H NMR, GC-MS, and LC-MS) and their current and potential use in critical care medicine.Source: This is a focused review, not a systematic review, using the PubMed database as the predominant source of references to compare metabolomics techniques.Principal Findings: 1 H NMR, GC-MS, and LC-MS are complementary techniques that can be used on a variety of biofluids for metabolomics analysis of patients in the Intensive Care Unit (ICU). These techniques have been successfully used for diagnosis and prognosis in the ICU and other clinical settings; for example, in patients with septic shock and community-acquired pneumonia. Conclusion:Metabolomics is a powerful tool that has strong potential to impact diagnosis and prognosis and to examine responses to treatment in critical care medicine through diagnostic and prognostic biomarker and biopattern identification. REVIEW ARTICLE © 2014 CIMClin Invest Med • Vol 37, no 6, December 2014 E363 Metabolomics refers to the systems level analysis of the metabolism and metabolites in response to physiological stimuli, such as disease or drug administration [1]. The application of clinical metabolomics to the complex illnesses of critical care medicine is relatively new [1,2]. Metabolomics, which is most commonly based on nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS) and/or liquid chromatography-mass spectrometry (LC-MS) platforms, provides an accurate reflection of the metabolic processes and pathways at play within the human body at a particular moment in time [1]. History of metabolomicsWhile the terms metabolomics and metabonomics are now used interchangeably, their original definitions focused on the level of analysis and the type of analytical technology used. This paper uses the term metabolomics as the terms are often treated as interchangeable and it is more commonly used in the literature than the term metabonomics [1,2]. Nicholson, who first defined metabonomics in 1999, described it as a systemsbased strategy to "measure the global, dynamic metabolic response of living systems to biological stimuli or genetic manipulation" [2]. Conversely, metabolomics was defined as the identification, analysis, and quantification of each metabolite within a biosample [3]. Metabolomics and metabonomics can also be defined by their method of analysis: metabolomics was originally described as a GC-MS-based approach in the study of plant metabolomes [3] and metabonomics was originally defined as NMR-based study of mammalian systems [2]. Although metabolomics and metabonomics were not defined until the late 1990s, biofluid analysis by GC-MS was first reported in the 1960s and 1970s [4]. The basis of today's metabolomics field started in the early 1980s, when NMR technology became adequately sensitive for biofluid metabolite identification. Combined with the use of statisti...

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Metabolomics as a Novel Approach for Early Diagnosis of Pediatric Septic Shock and Its Mortality

Cited by 167 publications

References 48 publications

Urinary 1H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis

Urinary 1H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis

Metabolomics: Applications and Promise in Mycobacterial Disease

Metabolomics in critical care medicine: a new approach to biomarker discovery

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